This project is a live imaging and interventional approach to study the molecular mechanisms of cerebral cortical development. Mental retardation in several diseases and syndromes such as Downs syndrome and autism may be a result of environmental or genetic alterations in prenatal cortical proliferation. To better understand how proliferation is controlled during brain development, molecular biology and virology will be combined with a novel organotypic culture of the neocortex to establish that glutamate, GABA, and bFGF can affect neocortical growth by changing the proliferative properties of neuronal progenitor cells. In addition, it will be determined, through a mutagenic approach, whether these extracellular molecules act via the Notch pathway of signal transduction, an intracellular mechanism for the control of neuroprogenitor proliferation.